Interaction of Ethylenediamine 2-pyridinecarboxcylatopalladium(II) nitrate with CT-DNA/BSA and its anti-tumor activity

Cis-Diamminedicholoroplatinum (II) (cisplatin), first identified as antitumor drug in late 1960. Thousand’s analog of this compound has been synthesized, characterized and tested for their antitumor activities. It has been reported that many active complexes could react with DNA and inhabit its synthesis1. The long-term application of Pt complexes is thwarted by issues, leading scientists to examine other metals such as palladium, which could exhibit complementary modes of action (given emphasis wherever known). Several research groups have focused on the application of an eclectic array of palladium complexes as potential anti-cancer agents2.In this study, a new palladium (II) complex of formula [Pd (en)(2-pyc)]NO3 (where en is 1,2-diaminoethane and 2-pyc is 2-pyridinecarboxylate anion) has been designed, synthesized and characterized. We selected 2-pyc as ligand because of its planar π aromatic moiety which assisted the interaction of the complex with bio macromolecules specially DNA3. The synthesized complex has been characterized by elemental analysis, conductivity measurements, and UV-Vis, FT-IR and 1H NMR spectroscopic techniques. The interaction of this complex with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) has been investigated using UV-Vis spectroscopy in 30 mmol/L Tris-HCl buffer of pH = 7.00 at two different temperatures of 300 and 310 K. In these studies, Kapp, apparent association constant was found to be 1.3 ×104 M–1 and 1.9 ×105 M–1 for DNA and 1.5 ×104 M–1 and 1.1 ×105 M–1 for BSA at 300 and 310 K, respectively. These results indicate that the titled complex can interact with DNA as well as BSA with moderately binding affinity. Furthermore, the concentration of the Pd(II) complex in the midpoint of transition from native to denatured DNA or BSA, [L]1/2, was calculated which increased from 0.034 mM to 0.038 mM for DNA and from 0.023 mM to 0.036 mM for BSA by increasing the temperature from 300 to 310 K. Moreover, the thermodynamic parameters (ΔG°, ΔS° and ΔH°) for the interaction of the complex with DNA and BSA have been calculated using the Kapp values and van’t Hoff equation. The in-vitro antitumor properties of the Pd (II) complex against human tumor cell line K562 were examined using MTT assay. The 50% cytotoxic concentration (Cc50) of the complex was determined 32 μM, indicating its potential anticancer activity, possibly targeting DNA.